Abstract
Certain proteins have demonstrated proficient human immunodeficiency virus (HIV-1) life cycle disturbance. Recently, the ankyrin repeat protein targeting the HIV-1 capsid, AnkGAG1D4, showed a negative effect on the viral assembly of the HIV-1NL4-3 laboratory strain. To extend its potential for future clinical application, the activity of AnkGAG1D4 in the inhibition of other HIV-1 circulating strains was evaluated. Chimeric NL4-3 viruses carrying patient-derived Gag/PR-coding regions were generated from 131 antiretroviral drug-naïve HIV-1 infected individuals in northern Thailand during 2001–2012. SupT1, a stable T-cell line expressing AnkGAG1D4 and ankyrin non-binding control (AnkA32D3), were challenged with these chimeric viruses. The p24CA sequences were analysed and classified using the K-means clustering method. Among all the classes of virus classified using the p24CA sequences, SupT1/AnkGAG1D4 demonstrated significantly lower levels of p24CA than SupT1/AnkA32D3, which was found to correlate with the syncytia formation. This result suggests that AnkGAG1D4 can significantly interfere with the chimeric viruses derived from patients with different sequences of the p24CA domain. It supports the possibility of ankyrin-based therapy as a broad alternative therapeutic molecule for HIV-1 gene therapy in the future.
Highlights
Despite the success of human immunodeficiency virus (HIV-1) treatment using highly active antiretroviral therapy (HAART), the complete elimination of the HIV-1 virus from the patient’s body is still not possible
The gene encoding the Gag/PR protein from the patients was obtained by reverse transcription-PCR (RT-PCR), as previously described [26], starting from HXB2 at nt. 623 to
The results showed that the mean p24 capsid domain (p24CA) level in
Summary
Despite the success of human immunodeficiency virus (HIV-1) treatment using highly active antiretroviral therapy (HAART), the complete elimination of the HIV-1 virus from the patient’s body is still not possible. The toxicity or side effects of antiretroviral drugs result in a decreased quality of life for infected people [1,2,3,4] For these reasons, alternative approaches for HIV-1 therapy are required. Protein therapy is a promising technique that has become an integral and significant part of current medical treatment Good examples of this next-generation medicine are antibodies and their engineered versions, such as bispecific or multispecific antibodies [5,6,7,8]. In this past decade, during which in vitro selection technology was developed, the selection of a binding protein without immunisation became possible. This led to many non-immunoglobulin scaffold proteins being characterised, used, and engineered to obtain a specific binding candidate [8,9,10]
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